You might think Jeremy Piven would be feeling on top of his game. Born in Manhattan and raised near Chicago, the actor has notched up three Emmy awards and a Golden Globe for his role as cut-throat agent Ari Gold – surely one of the decade's most memorable TV characters – in the ultimate comedy of Hollywood manners, Entourage. And while he waits for filming to start on the seventh series, Piven has a new Hollywood film to promote, the abrasive comedy The Goods: Live Hard, Sell Hard, described as "a homage to used-car salesmen everywhere".

And yet this 44-year-old actor – youthful and energetic enough to be in his prime – responds to even the most innocent questions with the edginess of an escaped convict. He is prone to viewing mild or even neutral statements about himself as veiled criticisms, or out-and-out attacks. Typically arriving at interviews with a handful of prepared lines, he quickly grows uncomfortable when he catches himself straying from them.

When singing the praises of fellow cast members, or talking about how much he loves British comedy – guess what, he's a huge fan of the original Office – he's on relatively solid ground. But, almost without prompting, Piven ties himself up in knots complaining that American journalists (and even American audiences) don't understand him or worrying that he doesn't have a new part lined up for the next few months.

Perhaps it is nerves. More likely, it's a reaction to the unusually rough ride he has had from the American press and his fellow actors since his clamorous exit from a Broadway production of David Mamet's Speed-the-Plow 10 months ago. Piven claimed he had mercury poisoning; his producers and co-stars suspected otherwise. A protracted arbitration process has only recently vindicated him.

It's fair to say that people in showbusiness don't always say the nicest things about Piven. His co-star in Speed-the-Plow, Raul Esparza, addressing the audience the night after Piven's withdrawal from the show last December, crowed that he didn't have to perform with "a big TV star" any more. William Macy, one of the actors who ended up replacing Piven, also had unkind words about actors who give up on their commitments. Mamet himself positively skewered Piven's story about contracting mercury poisoning from an excess of fish in his diet. "My understanding," the playwright said, in what has already come to be regarded as one of the great theatrical putdowns, "is that he is leaving showbusiness to pursue a career as a thermometer."

Piven remains deeply hurt by the whole episode, insisting his illness was entirely genuine (although he also hints at "other health factors", before hastily stopping himself). Dropping out, he says, was the last thing on his mind when he took the part and launched it to critical acclaim last October. "[Quitting the show] was a complete anomaly in my life and my career. I've never missed out on anything. I relished the opportunity to be on Broadway . . . It's the holy grail for people like me.

"But I was incredibly ill. The levels of mercury I had, they had no reference for them. I had to be retested three times. Sometimes when you work without stopping, your body gives in. That is what happened."

Even after Piven's vindication, a tongue-in-cheek lead paragraph in the tabloid New York Post proclaimed: "An arbitrator bought Jeremy Piven's fish tale hook, line and sinker." To which Piven responded with more prickliness. "Think about it for a second. You go to arbitration, wait a year and people still don't believe you. That's kind of funny, isn't it?"

It feels like there are two ways to view the Jeremy Piven phenomenon, and it is perhaps his bad luck that there is no reconciling the two.

The first is to see him as an unswervingly patient, jobbing actor who is finally getting his due. That is the version Piven himself prefers, of course – the kid who was on stage from the age of eight but only decided in college that he wanted to go into the family business (his parents founded the highly regarded Piven Theatre, whose alumni include John and Joan Cusack, Aidan Quinn and Rosanna Arquette), then slogged his way through endless auditions, rejections, bit parts and "breakout parts" that didn't quite live up to their promise.

"I've done more movies than years I've been alive," he says, and it's true. He has about 50 feature film credits, of which only one before now has been a lead, the forgotten 1994 college comedy PCU (Politically Correct University).

"All I've done is work . . . I arrived in Los Angeles in my early 20s and I've been pounding the pavement ever since. But it wasn't until Entourage that my work became accessible to so many people. If there's one thing I'm prepared for, it's rejection."

In the alternate version of Piven's life and career, he is more of a chancer who struck lucky once and is now racing against the clock to capitalise on his success in Entourage. Whatever the outcome of his arbitration, he has blown his chances of getting back on Broadway any time soon – as he himself puts it: "You can only hope to be given the opportunity to do it again."

His unpopularity around LA as well as New York has not helped. As one Hollywood producer put it to me: "His problem is that he's not as talented as he thinks he is."

It was his role as an engagingly slick-talking rogue in Entourage that finally put Piven on the map after two decades in the relative wilderness. These days, one of his complaints is that people have a habit of confusing him with the hard-charging Ari Gold. "People are sometimes disappointed I'm not going to yell and bitch and be a fire-breathing abusive narcissist pig. I'm just a stage actor from Chicago." But at least it is a complaint born of success, not failure.

At one point in our protracted interview (spanning two months of endless delays and deferred appointments, resulting in one abortive face-to-face meeting and, eventually, a longer phone call), Piven rails against the idea that there was any family favouritism involved in his casting in The Goods – even though the film was produced by his brother-in-law, the lowbrow comedy actor-director Adam McKay (previously responsible for Anchorman, Talladega Nights and Step Brothers).

"You can throw nepotism out of the window," Piven says with remarkable vehemence. "Adam has produced one hit after another in the past, and I wasn't even sniffing the sandwiches on those sets."

Yet intriguingly, it was Piven himself who mentioned that McKay was his brother-in-law. He launched into his nepotism rebuttal without actually being challenged about it.

His part in The Goods is not a million miles away from Ari the alpha male. His character, a freelance hustler named Don Ready, is silver-tongued enough to be able to sell just about anything, including a lot full of cars in a recession-hit suburb. Piven has high hopes that the film will resonate in these financially straitened times – in Britain if not in his native US.

"The film may be a lowbrow gonzo romp," he admits, "but it also offers real insight into the tragedies of the characters, and the whole phenomenon of jingoistic Americans butting into each other. You Brits have a reference and a real appreciation for this kind of dark comedy. Here, it's not as widespread."

That way of talking about The Goods perhaps feeds into the second, less charitable view of Piven. Put bluntly, he sounds, when he talks, like he's trying just too hard.

But he has been unlucky, too. The marketing division of Paramount ­ Vantage, the studio behind The Goods, was shut down earlier this year, and the movie was effectively dumped on the US market with only a half-hearted marketing push. Then American critics were lukewarm – one yawned that Piven "seemed a little too practised at this sort of wheeler-dealer" – and the film made only a fraction of the box office returns enjoyed by the summer's big comedy hit, Las Vegas bachelor romp The Hangover (even though one can argue that The Goods is quite a bit funnier).

"It was not the most ideal timing, obviously," Piven says, with some understatement, of the Paramount Vantage disaster. He can only hope things look a little brighter after it opens in Britain.